We have developed the chemistry to conjugate a pyrroloindole tripeptide (CDPI3) analog of CC-1065 to the 5' or 3' ends of any oligodeoxyribonucleotide (ODN). The resultant conjugates hybridize sequence specifically to complementary DNA and RNA strands, yet do not interact with double-stranded DNA. The conjugated CDPI3 moiety can significantly stabilize short duplexes by binding to the minor groove. In light of these results, we propose to evaluate the potential of these conjugates as anti sense and antigene agents. The ability of ODN-CDPI3 conjugates to sequence specifically inhibit replication, transcription and translation will be investigated using simple in vitro model systems. Limited cell culture studies will be initiated to evaluate the potential of these modified ODNs for use as anti sense, anti-viral or anti-cancer agents. PROPOSED COMMERCIAL APPLICATION: Modified ODNs which form unusually stable hybrids usually elicit increased potency when used as antisense or antigene agents. Oligomers linked to a CC-1065-like minor groove binder form unusually stable hybrids. If these ODNs effectively block replication, transcription or translation in a sequence specific fashion, their commercial potential will be very high.